Natural Killer (NK) cells are activated when they don't receive inhibitory signals, as indicated by the reference: "Natural killer cells function based on the signaling processes that involve their activating and inhibitory receptors. They activate when signals that prevent them from attacking (like MHC class I molecules) are absent or downgraded on a target cell." In simpler terms, NK cells are constantly checking other cells. If they detect a cell that is missing or has reduced levels of specific "don't attack me" signals, they become activated and attack that cell.
Here’s a more detailed look:
How NK Cells Recognize Targets
The activation of NK cells is a fine balance between activating and inhibitory signals.
Inhibitory Signals
- MHC Class I Molecules: Healthy cells display MHC class I molecules on their surface. These molecules act like flags that tell NK cells "I'm normal, don't attack."
- Mechanism: NK cells have inhibitory receptors that bind to MHC class I molecules. This binding sends a negative signal that prevents NK cell activation.
- Reduced MHC Class I: Cells that are infected by viruses or are cancerous often reduce the number of MHC class I molecules on their surface. This reduction means there is less of the "don't attack" signal.
Activating Signals
- Absence of MHC Class I: If a cell has significantly reduced or no MHC class I molecules, the NK cell will not receive the inhibitory signals. This lack of inhibition can trigger the NK cell to activate.
- Stress Ligands: Cells under stress (e.g., due to viral infection or cancer) may display stress ligands on their surface. Activating receptors on NK cells can bind to these stress ligands.
- Antibody-Dependent Cellular Cytotoxicity (ADCC): NK cells can also be activated by antibodies that have bound to a target cell, a process known as ADCC.
The Activation Process
When an NK cell encounters a cell with reduced MHC class I molecules or displays activating signals:
- Reduced Inhibition: The NK cell receives weaker inhibitory signals than usual due to the absence or downgrade of MHC class I.
- Activation: Activating receptors on the NK cell bind to the ligands on the target cell or an antibody, sending a positive activation signal.
- Attack: The balance tips in favor of activation, and the NK cell releases cytotoxic granules containing proteins (like perforin and granzymes) that induce the target cell's death.
Summary of NK Cell Activation
Condition | MHC Class I Levels | NK Cell Response |
---|---|---|
Healthy Cell | Normal/High | Inhibited |
Virally Infected/Cancerous Cell | Reduced/Absent | Activated |
Presence of stress ligands | Any level | Activated |
Antibody-coated target cell | Any level | Activated |
Practical Implications
- Immune Surveillance: This mechanism allows NK cells to detect and eliminate cells that are becoming cancerous or infected, playing a critical role in immune surveillance.
- Cancer Therapy: Understanding how NK cells activate can help develop new cancer treatments by enhancing NK cell activity against cancer cells.
- Viral Infections: NK cells are a first line of defense against viral infections and work to eliminate infected cells.